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Malignant migrating partial seizures of infancy

Malignant migrating partial seizures of infancy (MMPSI) is a severe form of epilepsy
that begins very early in life. Recurrent seizures begin before the age of 6 months
but commonly start within a few weeks of birth. The seizures do not respond well to
treatment. Although affected individuals may develop normally at first, progression stalls
and skills decline when seizures begin; as a result, affected individuals have profound
developmental delay.
The seizures in MMPSI are described as partial (or focal) because the seizure activity
occurs in regions of the brain rather than affecting the entire brain. Seizure activity can
appear in multiple locations in the brain or move (migrate) from one region to another
during an episode. Depending on the region affected, seizures can involve sudden
redness and warmth (flushing) of the face; drooling; short pauses in breathing (apnea);
movement of the head or eyes to one side; twitches in the eyelids or tongue; chewing
motions; or jerking of an arm, leg, or both on one side of the body. If seizure activity
spreads to affect the entire brain, it causes a loss of consciousness, muscle stiffening,
and rhythmic jerking (tonic-clonic seizure). Episodes that begin as partial seizures and
spread throughout the brain are known as secondarily generalized seizures.
Initially, the seizures associated with MMPSI are relatively infrequent, occurring
every few weeks. Within a few months of the seizures starting, though, the frequency
increases. Affected individuals can have clusters of five to 30 seizures several times
a day. Each seizure typically lasts seconds to a couple of minutes, but they can be
prolonged (classified as status epilepticus). In some cases, the seizure activity may
be almost continuous for several days. After a year or more of persistent seizures, the
episodes become less frequent.
Seizures can affect growth of the brain and lead to a small head size (microcephaly).
The problems with brain development can also cause profound developmental delay
and intellectual impairment. Affected babies often lose the mental and motor skills they
developed after birth, such as the ability to make eye contact and control their head
movement. Many have weak muscle tone (hypotonia) and become "floppy." If seizures
can be controlled for a short period, development may improve. Some affected children
learn to reach for objects or walk. However, most children with this condition do not
develop language skills.
Because of the serious health problems caused by MMPSI, many affected individuals
do not survive past infancy or early childhood.

Frequency
MMPSI is a rare condition. Although its prevalence is unknown, approximately 100
cases have been described in the medical literature.
Causes
The genetic cause of MMPSI is not fully known. Mutations in the KCNT1 gene have
been found in several individuals with this condition and are the most common known
cause of MMPSI. Mutations in other genes are also thought to be involved in the
condition.
The KCNT1 gene provides instructions for making a protein that forms potassium
channels. Potassium channels, which transport positively charged atoms (ions) of
potassium into and out of cells, play a key role in a cell's ability to generate and transmit
electrical signals. Channels made with the KCNT1 protein are active in nerve cells
(neurons) in the brain, where they transport potassium ions out of cells. This flow of
ions is involved in generating currents to activate (excite) neurons and send signals in
the brain.
KCNT1 gene mutations alter the KCNT1 protein. Electrical currents generated by
potassium channels made with the altered KCNT1 protein are abnormally increased,
which allows unregulated excitation of neurons in the brain. Seizures develop
when neurons in the brain are abnormally excited. It is unclear why seizure activity
can migrate in MMPSI. Repeated seizures in affected individuals contribute to the
developmental delay that is characteristic of this condition.

Inheritance Pattern
MMPSI is not inherited from a parent and does not run in families. This condition is
caused by a new mutation that occurs very early in embryonic development (called a de
novo mutation).

Other Names for This Condition

• early infantile epileptic encephalopathy 14
• EIEE14
• malignant migrating partial epilepsy of infancy
• migrating partial epilepsy of infancy
• migrating partial seizures in infancy
• migrating partial seizures of infancy
• MMPSI

Diagnosis & Management

Genetic Testing Information
• What is genetic testing?
/primer/testing/genetictesting
• Genetic Testing Registry: Early infantile epileptic encephalopathy 14
https://www.ncbi.nlm.nih.gov/gtr/conditions/C3554195/

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 Research Studies from ClinicalTrials.gov
• ClinicalTrials.gov
https://clinicaltrials.gov/ct2/results?cond=%22malignant+migrating+partial+seizures
+of+infancy%22+OR+%22early+infantile+epileptic+encephalopathy%22

Other Diagnosis and Management Resources

• GeneReview: KCNT1-Related Epilepsy
https://www.ncbi.nlm.nih.gov/books/NBK525917
• MedlinePlus Encyclopedia: EEG
https://medlineplus.gov/ency/article/003931.htm

Additional Information & Resources

Health Information from MedlinePlus
• Encyclopedia: EEG
https://medlineplus.gov/ency/article/003931.htm
• Encyclopedia: Epilepsy
https://medlineplus.gov/ency/article/000694.htm
• Encyclopedia: Partial (Focal) Seizure
https://medlineplus.gov/ency/article/000697.htm
• Health Topic: Epilepsy
https://medlineplus.gov/epilepsy.html
• Health Topic: Seizures
https://medlineplus.gov/seizures.html

Genetic and Rare Diseases Information Center

• Malignant migrating partial seizures of infancy
https://rarediseases.info.nih.gov/diseases/12919/malignant-migrating-partial-
seizures-of-infancy

Additional NIH Resources

• National Institute of Neurological Disorders and Stroke: Epilepsy
https://www.ninds.nih.gov/Disorders/All-Disorders/Epilepsy-Information-Page

Educational Resources
• Boston Children's Hospital: Seizures
http://www.childrenshospital.org/conditions-and-treatments/conditions/s/seizures
• Centers for Disease Control and Prevention: Developmental Disabilities
https://www.cdc.gov/ncbddd/developmentaldisabilities/facts.html
• Epilepsy Action: Migrating Partial Epilepsy in Infancy
https://www.epilepsy.org.uk/info/syndromes/migrating-partial-epilepsy-in-infancy

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 • KidsHealth from Nemours: Seizures
https://kidshealth.org/en/parents/seizure.html
• MalaCards: malignant migrating partial seizures of infancy
https://www.malacards.org/card/malignant_migrating_partial_seizures_of_infancy
• Orphanet: Malignant migrating focal seizures of infancy
https://www.orpha.net/consor/cgi-bin/OC_Exp.php?Lng=EN&Expert=293181
• World Health Organization: Epilepsy
https://www.who.int/en/news-room/fact-sheets/detail/epilepsy

Patient Support and Advocacy Resources

• CURE Epilepsy
https://www.cureepilepsy.org/
• Medical Home Portal: Seizures/Epilepsy
https://www.medicalhomeportal.org/diagnoses-and-conditions/seizures-epilepsy

Clinical Information from GeneReviews

• KCNT1-Related Epilepsy
https://www.ncbi.nlm.nih.gov/books/NBK525917

Scientific Articles on PubMed

• PubMed
https://www.ncbi.nlm.nih.gov/pubmed?term=%28%28malignant+migrating+pa
rtial+seizures+of+infancy%29+OR+%28early+infantile+epileptic+encephalopathy
+14%29%29+AND+english%5Bla%5D+AND+human%5Bmh%5D+AND+%22last
+2520+days%22%5Bdp%5D

Catalog of Genes and Diseases from OMIM

• EPILEPTIC ENCEPHALOPATHY, EARLY INFANTILE, 14
http://omim.org/entry/614959

Sources for This Summary

• Barcia G, Fleming MR, Deligniere A, Gazula VR, Brown MR, Langouet M, Chen H, Kronengold J,
Abhyankar A, Cilio R, Nitschke P, Kaminska A, Boddaert N, Casanova JL, Desguerre I, Munnich
A, Dulac O, Kaczmarek LK, Colleaux L, Nabbout R. De novo gain-of-function KCNT1 channel
mutations cause malignant migrating partial seizures of infancy. Nat Genet. 2012 Nov;44(11):
1255-9. doi: 10.1038/ng.2441. Epub 2012 Oct 21.
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23086397
Free article on PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3687547/
• Coppola G. Malignant migrating partial seizures in infancy: an epilepsy syndrome of unknown
etiology. Epilepsia. 2009 May;50 Suppl 5:49-51. doi: 10.1111/j.1528-1167.2009.02121.x. Review.
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/19469847

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 • Ishii A, Shioda M, Okumura A, Kidokoro H, Sakauchi M, Shimada S, Shimizu T, Osawa M, Hirose
S, Yamamoto T. A recurrent KCNT1 mutation in two sporadic cases with malignant migrating partial
seizures in infancy. Gene. 2013 Dec 1;531(2):467-71. doi: 10.1016/j.gene.2013.08.096. Epub 2013
Sep 10.
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/24029078
• McTague A, Appleton R, Avula S, Cross JH, King MD, Jacques TS, Bhate S, Cronin A, Curran
A, Desurkar A, Farrell MA, Hughes E, Jefferson R, Lascelles K, Livingston J, Meyer E, McLellan
A, Poduri A, Scheffer IE, Spinty S, Kurian MA, Kneen R. Migrating partial seizures of infancy:
expansion of the electroclinical, radiological and pathological disease spectrum. Brain. 2013 May;
136(Pt 5):1578-91. doi: 10.1093/brain/awt073. Epub 2013 Apr 18.
Citation on PubMed: https://www.ncbi.nlm.nih.gov/pubmed/23599387
Free article on PubMed Central: https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3634200/

Reprinted from Genetics Home Reference:

https://ghr.nlm.nih.gov/condition/malignant-migrating-partial-seizures-of-infancy

Reviewed: March 2014

Published: October 29, 2019

Lister Hill National Center for Biomedical Communications

U.S. National Library of Medicine
National Institutes of Health
Department of Health & Human Services

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